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Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression
Ahmed, Suhail Kurusamy, Sathishkumar David, Ezra Leander Santhosh Khan, Kinza Kalyanakrishnan, Krithika Ian-Gobo, Miebaka Kola, Teja Manidhar Wilkinson, Robert N Kannappan, Vinodh Wang, Weiguang
Ahmed, Suhail
Kurusamy, Sathishkumar
David, Ezra Leander Santhosh
Khan, Kinza
Kalyanakrishnan, Krithika
Ian-Gobo, Miebaka
Kola, Teja Manidhar
Wilkinson, Robert N
Kannappan, Vinodh
Wang, Weiguang
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2022-08-30
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Abstract
Angiogenesis is a multi-factorial physiological process deregulated in human diseases characterised by excessive or insufficient blood vessel formation. Emerging evidence highlights a novel role for microRNAs as regulators of angiogenesis. Previous studies addressing the effect of miR-133a expression in endothelial cells during blood vessel formation have reported conflicting results. Here, we have assessed the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. Transfection of miR-133a-3p or -5p mimics in primary human endothelial cells significantly inhibited proliferation, migration, and tubular morphogenesis of transfected cells. Screening of gene arrays related to angiogenic processes, and further validation by TaqMan qPCR, revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a collection of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. Our results suggest that controlled delivery of miR-133a-3p mimics, or antagomirs in diseased endothelial cells, might open new therapeutic interventions to treat patients suffering from cardiovascular pathologies that occur with excessive or insufficient angiogenesis.
Citation
Ahmed, S., Kurusamy, S., David, E.L.S. et al. (2022) Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by reducing pro-angiogenic but increasing anti-angiogenic gene expression. Scientific Reports 12, 14730. https://doi.org/10.1038/s41598-022-19172-x
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Journal article
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en
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© 2022 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41598-022-19172-x
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2045-2322
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2045-2322
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This work was supported by the Research Institute in Healthcare Sciences, Faculty of Science and Engineering, University of Wolverhampton (to A.L.A) and by generous donations from the charities “Wolverhampton Coronary Aftercare Support Group” (to A.L.A and J.C) and “Rotha Abraham Bequest” (to A.L.A and J.C). S.A. is the recipient of a University of Wolverhampton-Wolverhampton Royal NHS Trust joint PhD studentship. JMR has received funding from the “La Caixa” Banking Foundation HR18-00068 (to J.M.R.); Spanish Ministerio de Ciencia e Innovación grant RTI2018-099246-B-I00 (MICIU/AEI/FEDER, UE) to J.M.R and the Instituto de Salud Carlos III (CIBER-CV CB16/11/00264) to J.M.R. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro-CNIC Foundation.